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Biomedical subjects

G Fisch

Publications and source records attributed to G Fisch.

13 recordsLinked to original sources
PubMed2006

A novel siRNA-lipoplex technology for RNA interference in the mouse vascular endothelium.

For the application of RNA interference (RNAi) in vivo the functional delivery of short interfering RNAs (siRNAs) is still the major obstacle. Therefore, delivery technologies need to be established for the systemic application of RNAi in vivo. Here we report uptake, biodistribution and in vivo efficacy of siRNA molecules formulated into siRNA-lipoplexes. The applied formulation is based on complex formation of positively charged liposomes, a mixture of cationic and fusogenic lipids complexed with the negatively charged siRNA. We determined by fluorescence microscopy the temporal and spatial distribution of fluorescently labeled siRNA-lipoplexes, the body clearance and endothelial cell type specific uptake after single intravenous injection. Furthermore, by using siRNA molecules for targeting endothelia-specifically expressed genes, such as CD31 and Tie2, we were able to demonstrate downregulation of the corresponding mRNA and protein in vivo. Taken together, we show the applicability of this non-viral delivery technology for inducing RNAi in the vasculature of mice after systemic application.

Animals↗
PubMed2006

RNA interference in the mouse vascular endothelium by systemic administration of siRNA-lipoplexes for cancer therapy.

RNA interference (RNAi) entails the potential for novel therapeutic strategies through the silencing of disease-causing genes in vivo. However, recent studies have raised an issue regarding applicable routes of administration for small interfering RNA (siRNA) molecules as therapeutics. In this study, we demonstrate that liposomally formulated siRNA molecules, the so-called siRNA-lipoplexes, but not naked siRNAs, are delivered to the tumor endothelial cells in vivo by microscopy. In addition, functional intracellular delivery of formulated siRNA targeting the tumor suppressor PTEN is shown in endothelial cells of the liver and tumor. Finally, the therapeutic potential of systemically administered siRNA(CD31)-lipoplexes is established by inhibition of tumor growth in two different xenograft mouse models. Our findings corroborate the applicability of this liposomal siRNA delivery technology for inducing RNAi to modulate gene expression levels in angiogenesis-dependent processes. In addition, our results advocate CD31 as a promising therapeutic target for antiangiogenic intervention. Therefore, our study provides a basis for the development of antiangiogenic cancer therapies based on RNAi.

3T3 Cells↗
PubMed1979

[Results in the documentation for pregnancy surveillance].

Some results from the pregnancy surveillance booklet documentation are discussed in this paper. These results were gained on the basis of data from a representative random sample taken in Rheinland-Pfalz in 1977. Unfortunately, the risk factors section in the pregnancy surveillance booklet does not receive sufficient medical documentation. Apparently, its structure is too complex and its second part is not on the proper place. Contrary to the risk factor check list, which has been answered poorly, the entry of the observations on the course of the pregnancy obviously has carried out regularly. Only half of the pregnant women take advantage of at least 10 preventive medial examinations. Frequency of these examinations and date of the first medical examination in pregnancy depend on social conditions. In case of unfavourable general conditions pregnant women go less often, and later, to the prenatal examinations and the state of health of the new-born child depends on the "social strata" factor. Seen especially from the viewpoint of a greater centralization in obstetrics, the measures taken in prenatal care should be decentralized and varied and should include a revision of the pregnancy surveillance booklet.

Child Health Services↗